BAP1 as a guardian of genome stability: implications in human cancer

Jongbum Kwon, Daye Lee, Shin Ai Lee

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

BAP1 is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with a wide array of biological activities. Studies in which advanced sequencing technologies were used have uncovered a link between BAP1 and human cancer. Somatic and germline mutations of the BAP1 gene have been identified in multiple human cancers, with a particularly high frequency in mesothelioma, uveal melanoma and clear cell renal cell carcinoma. BAP1 cancer syndrome highlights that all carriers of inherited BAP1-inactivating mutations develop at least one and often multiple cancers with high penetrance during their lifetime. These findings, together with substantial evidence indicating the involvement of BAP1 in many cancer-related biological activities, strongly suggest that BAP1 functions as a tumor suppressor. Nonetheless, the mechanisms that account for the tumor suppressor function of BAP1 have only begun to be elucidated. Recently, the roles of BAP1 in genome stability and apoptosis have drawn considerable attention, and they are compelling candidates for key mechanistic factors. In this review, we focus on genome stability and summarize the details of the cellular and molecular functions of BAP1 in DNA repair and replication, which are crucial for genome integrity, and discuss the implications for BAP1-associated cancer and relevant therapeutic strategies. We also highlight some unresolved issues and potential future research directions.

Original languageEnglish
Pages (from-to)745-754
Number of pages10
JournalExperimental and Molecular Medicine
Volume55
Issue number4
DOIs
StatePublished - Apr 2023

Bibliographical note

Funding Information:
This work was supported by grants 2021R1A2C1008613 (JK), 2019R1A5A6099645 (JK) and 2022R1I1A1A01073047 (DL) from the National Research Foundation of Korea (NRF).

Publisher Copyright:
© 2023, The Author(s).

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